(D1)-thiophosphoric acid esters

ABSTRACT

Compounds of the formula   WHEREIN R1 and R2 are alkyl having from one to six carbon atoms; R3, R4, R5, R6, R7 are hydrogen or alkyl having from one to four carbon atoms; at least three of the radicals R3 to R7 being hydrogen; R8, R9 are hydrogen, halogen, alkyl or alkoxy each having from one to four carbon atoms; X is oxygen or sulfur. The compounds have a good activity against insects, acarides, nematodes and animal ectoparasites.

United States Patent [191 Hiirlein et al.

[ (Dl)-THIOPHOSPHORIC ACID ESTERS [75] Inventors: Gerhard Hiirlein, Frankfurt, Main;

Gerhard Salbeck, Kelkheim, Taunus, both of Germany [73] Assignee: Hoechst Aktiengesellschaft, Frankfurt, Main, Germany [22] Filed: July 10, 1973 211 App]. No.: 377,954

Related US. Application Data [63] Continuation-in-part of Ser. No. 293.l33, Sept. 28, 1973, abandoned, and a continuation-in-part of Ser. No 293,134, Sept. 28. i973, abandoned.

Primary ExaminerHenry R. Jiles Assistant Examiner-C. M. S. .laisle Attorney, Agent, or FirmCurtis, Morris & Safford May 13, 1975 [57] ABSTRACT Compounds of the formula wherein R and R are alkyl having from one to six carbon atoms;

R R R R R are hydrogen or alkyl having from one to four carbon atoms; at least three of the radicals R to R being hydrogen;

R R are hydrogen, halogen, alkyl or alkoxy each having from one to four carbon atoms;

X is oxygen or sulfur The compounds have a good activity against insects, acarides, nematodes and animal ectoparasites.

9 Claims, No Drawings (DD-THIOPHOSPHORIC AC ID ESTERS This application is a continuation-in-part of our copending applications Ser. Nos. 293,133 and 293,134, both filed Sept. 28, I972 and both now abandoned.

The present invention relates to compounds of the R R R R R are hydrogen or alkyl having from one to four carbon atoms; at least three of the radicals R to R being hydrogen;

R R, are hydrogen, halogen, alkyl or alkoxy each having from one to four carbon atoms;

X is oxygen or sulfur.

The compounds of formula I are prepared by reacting 4-halogeno-thiochromanyl compounds of the formula wherein Y is halogen, with phosphorus compounds of the formula 1;;sa (III) R or the salts thereof, if necessary in the presence of an acid binding agent.

The compounds of formula I have good insecticidal, acaricidal and nematocidal properties.

The present invention thus relates also to insecticidal, acaricidal and/or nematocidal products which contain a compound of formula I as active substance.

The reaction is generally carried out using about stoichiometric amounts of the reactants; a slight excess of Red.

the compound of formula 11] being advantageous. It is recommended to operate in the presence of a solvent inert under the reaction conditions. Such solvents are for example benzene or alkylbenzene, such as toluene or xylene; halogenobenzenes, such as chlorobenzene or dichlorobenzene; halogenated aliphatics, such as methylene chloride, chloroform, carbon tetrachloride, dichloro-ethane; ethers, such as diethyl ether, diisopropyl ether, glycol-dimethyl ether, tetrahydrofuran, dioxan, or ketones and nitriles, such as acetone, methylethylketone, methyl-isopropylketone, methylbutylketone, benzonitrile or propionitrile. Polar solvents are preferred.

The reaction temperatures are not critical and may be varied within wide limits, for example in a range of from 20 to C. Generally, room temperature or temperatures establishing themselves by the exothermic reaction are preferred.

The reaction proceeds with exchange of the halogen atom Y. Therefore, it is carried out either with addition of acid binding agents, or using salts, especially alkali metal or ammonium salts of the phosphorus compounds of formula Ill. Preferred acid binding agents are alkali metal hydroxides and alkali metal carbonates; but tertiary nitrogen bases, for example pyridine or triethylamine, may also be employed.

According to the process of the invention, the compounds of formula I are obtained with a very high yield and purity degree.

The starting compounds offormula III are known and can be easily prepared according to usual methods.

The 4-halogeno-thiochromanyl compounds of formula II and their preparation are partly described in French Pat. No. 1,584,755, partly they are novel compounds; also their pre-stages are in part new. They are prepared according to known processes by first reducing benzene sulfochlorides to the corresponding thiophenols. In a second reaction step, the thiophenols are reacted with substituted halogeno-propionic acids or l,2- unsaturated acids, and the phenylmercaptopropionic acids obtained are cyclized in the presence of dehydrating agents, for example concentrated sulfuric acid, polyphosphoric acid or phosphorus pentoxide, to form thiochromanones.

By reduction of the thiochromanones according to known processes, for example by means of sodium boron hydride or by a reduction according to Grignard, 4-hydroxy-thiochromane compounds are obtained which, also in known manner, are converted to the 4-halogeno-thiochromanyl compounds of formula ll with the aid of a halogenating agent, for example phosphorus trichloride, phosphorus tribromide, thionyl chloride, sulfuryl chloride or halogen hydracids. The reaction proceeds for example according to the follow' ing scheme:

(zoom c-n a 6 R c1z Rod. R Grignard agent As substituents R, and R any straight-chain or branched alkyl radicals having from one to six carbon atoms may be used, preferably methyl, ethyl, n-propyl or isopropyl.

Preferred radicals R to R are hydrogen, methyl or ethyl. Examples or R and R are: fluorine, chlorine, bromine, methyl, ethyl, isopropyl, tertiary butyl; meth oxy, ethoxy, propoxy, tertiary butoxy.

The alkyl and alkoxy groups contain preferably one to two carbon atoms. Advantageous are combinations wherein both radicals R and R are hydrogen, or one of these radicals at least is chlorine or bromine.

The compounds of formula I are suitable for the destruction of numerous pests of the different crop plants including their development stages, and they have an insecticidal as well as an acaricidal activity. Thus, different spider mite species, for example the European red mite (Metatetranychus ulmi), or mites like Panonychus cim' or Tetranychus urticae, among them also strains resistant to phosphoric esters can be controlled with good results.

Also numerous biting and sucking insects noxious to crop plants can be destroyed by the compounds of the invention, for example beetles, such as the Mexican bean beatle (Epilaclma variveslis), the Colorado beetle (Leptinotarsa decemlineala), the flower beetle (Epicomeris hirra), the flea beetle (Phyllolreta spp.), the strawberry borer (Coenorrhinus germanicus), or the boll weevel (Anrhonomus grandis); butterflies and their larvae, such as the Egyptian and the Old World boll worm (Earius insulana and Heliothis armz'gera); leaf rol lers, especially the codling moth (Carcocapsu pornonella), the green oak leaf roller (Torlrix viridana), the tortrix moth ((apua rericulrma), the corn borer (Ostriniu nubilalis) or the winter moth (Cheimatobia bmmara); aphids, such as the bean aphid (Doralis fabue), the green peach aphid (Myzodes persicae), the cotton aphid (Aphis gossypii); or bugs, such as milkweed bugs and cotton stainers (Oncupellus fasciatus and Dysdercus rpp., especially fasciatus).

The compounds are furthermore useful for the combating of animal ectoparasites. The term ectoparasites" as herein used refers to members of the phylum Arthropoda and, more exactly, of the class lnsecta (insects) and the order Acarina (ticks and mites) that live on the surface of warm-blooded animals and, as bloodsuckers, irritants and carriers of infectious diseases, may cause extensive damage in stock-farming.

Among the animal ectoparasites of the insect class against which the compounds of formula I are active are lice (Haematopinidae), fleas (Ceratophyllidae), maallopaga, furthermore flies, especially gad flies (Stomoxydinae) and horse flies (Tabanidae), those flies the development stages (larvae) of which parasite in the animal body (Calliphoridae, Sarcophagidae, Gastrophilidae, Oestridae), and louse flies (Hippobascidae). Among the ectoparasites of the mite class (Acari) are sarcoptides (Sarcoptidae), dermanyssides (Dermanyssidae), argasides (Argasidae) and ixodides (Ixodidae), especially the monoxenous cattle ticks Boophilus microplus and Boophilus decoloratus, and the heteroxenous species of the genus Rhipicephalus, Ablyomma and Hyalomma.

The compounds of the invention are also suitable for combating certain nematode species noxious to plants.

They are of low toxicity to warmblooded animals and partly have a very low toxicity to fish, so that they may be applied for example for combating infectioncarrying mosquitoes (yellow fever mosquitoes, anopheles) in their larval stage.

On account of their different chemical structure, the compounds of the invention may also be used for combating such strains of organisms which are resistant to other biocides.

The phosphoric acid esters of the present invention may be formulated in admixture with solid or liquid inert carrier substances, adhesives, wetting and dispersing agents, or grinding auxiliaries in the form of wettable powders, emulsions, suspensions, dusting powders, granules, fly-bands, products for spreading and washing. They may be mixed with other insecticides, fungicides, nematocides and herbicides. When used as ectoparasiticides, they are applied normally by spraying, dusting or dipping methods, as well as, in the special case of the anti-tick agents, in the so-called dip or spray equipment.

As carrier material, mineral substances may be used, for example aluminum silicates, argillaceous earths, ka-

olin, chalks, siliceous chalks, talcum, kieselguhr or hydrated silicic acids, or preparations of these mineral substances with special additives, for example chalk with sodium stearate. As carrier material for liquid preparations, all usual and suitable organic solvents may be employed, for example toluene, xylene, diacetone alcohol, isophorone, gasolines, paraffin oils, dioxan, dimethyl formamide, dimethyl sulfoxide, ethyl acetate, butyl acetate, tetrahydrofuran, chlorobenzene and the like.

Suitable adhesives are glue-like cellulose products or polyvinyl alcohols.

As wetting agents, all suitable emulsifiers may be used, for example ethoxylated alkylphenols, salts of arylor alkyl-aryl-sulfonic acids, salts of oxethylated benzenesulfonic acids, or soaps.

Suitable dispersing agents are cellulose pitch (salts of sulfite cellulose waste liquor), salts of naphthalenesulfonic acid or, in certain cases, hydrated silicic acids or kieselguhr.

As grinding auxiliaries, suitable inorganic or organic salts, for example sodium sulfate, ammonium sulfate, sodium carbonate and sodium bicarbonate, sodium thiosulfate, sodium stearate, or sodium acetate may be 6 g of active substance are ground with 6 g of finely dispersed silicic acid, and subsequently mixed in a mixer with 48 g ofa mixture containing 13.3% of dried' 2 g of active substance, 16 g of cyclohexanone and 2 g of alkylaryl-polyglycol ether alcohol are mixed with each other. g of a 10% emulsifiable concentrate are obtained.

The following Examples illustrate the invention. General prescription:

0.1 Mole of a halogeno-thiochromane of formula I1 is added, at room temperature and with agitation, to a solution or suspension of 0.10 to 0.1 1 mole of a dithiophosphate of formula III in 220 ml of glycol-dimethyl ether. Stirring is continued for about 15 hours at room temperature, the precipitated salt is separated by suction-filtration, the filtrate is diluted with about 400 m1 of benzene, the organic phase is thoroughly washed used. with water and dried over Na SO After having dis- The content of active substance in the ready-for-use tilled Off the Solvflht, the PrOdUCtS 0f the Process are products is generally from 2 to 95%. obtained as oils which, in part, crystallize on tritura- Simple formulations suitable for the activity tests tiOn. may be obtained in the following manner: According to this process as indicated above, the fol- Wettable powder: lowing compounds are obtained:

1 1 Example Formula n or melting Yield i of Analysls th t1 a1 p fifi C Cale Found S i i v z 5 14 C 43 5 S-P(OCn- 29 5 6 6 1 4. 9 a 4 9 l D 22 9 10.15 P 10.0 (A 51.57 s 51.4

S s g/ h5 melting point 46. 7 C 46.2 5 7 i1 5 i 2 oc a 49-50 90 93 P 9.2 I G 28 7 S 29 7 S 49 72 C 50 4 u S--P(OC;,,H iSO 31 Q 6.55 11 6.4 5 D 1 9 #5 8.56 P 8,6 26. 52 l 5 2'7 v 1 Q p .5 5 l c 8 s-eioca 24 6 5.2 H 5.5 4 3 115818 8 10, 7 P 10. 2 22 O S 21 7 S O i H 8-? 0c H 49. 1 e 4e. 9 2 5 2 n 24 1,5701 a1 6.0 a 6.3 5 D 9 7 P 9 5 l S i n t'u F 5' 2 9. c- P 9 e 6 l w \OCH3 o 9 5 9O 29 6 s 30. 0

Continued l Example Formula n or melting Yield A of nalysis o heoretieal A Polnt C) yield Calc- Pound I ig melting point: 2- ic i l... l H 43 ec n 4950 85 8; P '3 "J S 27.6 S 8.:.

S 5 OCH 6 OCH 29.5 9. 9 P 9.0 44 @[fi Clg 5 o lisllz 95 50.0 s 29.8

S S i z s 48.28 c 49.0 2 6.05 5.1

O p 27.6 s 27.5 rfi-u -'w -S OCH C. H S-P l 46 5 cn 11 1,6028 90 i 28.7 s 26.?

T C F S i i 47 2 oc n 11 1.6128 88 26.5 s 26.8

l s 3 can l 48 ca oca n L6Ol 84 28.6 s 28.2

.-' S i S l 2 a 46.2 c 46.; Y n 29. 5.78 H 5. Cri k/ZHS DD 5 P 8 0 L 26.4 S 26.4

Examples of application: aphids (Doralis fabae) were sprayed, until beginning EXAMPLE 5O drip-off, with the aqueous dilution of an emulsifiable dia/inone til weight ll of AS 40% killing rate of mite population azinphos-cthyl (ll weight ii 669: killing rate of mite of AS population tlimethoute U l weight 92 of AS no effect dcmcton-S mcthyl (l.l weight 7r of AS no effect EXAMPLE 51 Horse beans (View fulm) heavily infested with bean concentrate containing 0.00075 weight of 4- thiochromanyl-0.0-diethyldithiophosphate as active substance. The sprayed plants were then placed at 20 C in a greenhouse; evaluation was carried out 24 hours after the spraying. All aphids were killed.

EXAMPLE 52 Larvae (4th stage) of the Mexican bean beetle (Epilachna varivestis) and leaves of the dwarf-bush bean (Phaseoius vulgaris) were sprayed, by means of a spraying apparatus, with a dosed amount (corresponding to an application amount of 600 liters of spray liquorlha in the open fields) of the aqueous dilution of an emulsifiable concentrate containing 4-thiochromanyl-t).(ldimethyl-dithiophosphate. The leaves and beetle larvae were placed in open vessels at 22 C. A concentration of 0.0012 mg of active substance was sufficient to kill all larvae after 48 hours.

EXAMPLE 53 Young apple trees planted in pots and heavily infested with a phosphoric ester resistant strain of the European red mite (Melaretrunychus ulmi) were sprayed. until beginning drip-off. with the aqueous dilution ofan emulsifiable concentrate containing 0.025 weight "/1 of 2-methyl-4-thiochromanyl0,0 diethyl-dithiophosphate as active substance and subsequently placed in a green house at C.

A microscopic control after 8 days showed that all mobile and immobile stages were killed.

The following commercial phosphoric acid esters used in comparative tests showed no activity at the same and even at higher concentration:

phenkapton 0.025 weight no effect demeton-S-methyl 0.05 do. do.

dimethoate 0.05 do. do.

EXAMPLE 54 lethal conccntr.

diazinonc 0.025 of AS dimecron 0,025 of AS dimethoate 0.025 70 of AS [AS active substance) ['70 weight azinphos-ethyl 0.05 of AS EXAMPLE 55 Caterpillars (3rd stage) of the white cabbage butter fly (Pieris brassicae) and leaves of white cabbage (Bra.r- .rica oleracea varv capitata) or Savoy cabbage (Brassica oleracea var. sabauda) were sprayed with an aqueous dilution of an emulsifiable concentrate of 3-methyl-4- thiochromanyl-0,0-dimethyldithiophosphate, and subsequently placed in open vessels in the laboratory at about 22 C.

A concentration of active substance of 0.005 weight or 0.003 mg/cm was sufficient to obtain a 100% kill of the caterpillars after 48 hours.

EXAMPLE 56 In the manner described in Example 54, the com pound 6 -methyl-4-thiochromanyl-0,0-dimethyldithiophosphate was tested on the African cotton stainer (Dysdercus fasciatus), in which test all bugs were killed within 48 hours using a concentration of 0.006 weight of active substance in the spray liquor.

EXAMPLE 57 About 7 weeks old larvae of the mealworm (Tenebrio moliror) on a substrate (filter paper) were sprayed with a dosed amount of an aqueous suspension of a wettable powder of 6-methyl-4- thi0chromanyl-O,0-dimethyl-dithiophosphate, and sub sequently placed in the laboratory on Petri dishes at about 22 C.

A concentration of 0.003 mg/cm of active substance was sufficient to kill all larvae within 48 hours.

EXAMAPLE 58 Larvae of the yellow fever mosquito, stage IV (Aedes aegypti) and other mosquito larvae, stage IV (Culex pipicns) were placed in beakers containing I00 ml of an aqueous dilution of a wettable powder concentrate, the concentration of 6-fluoro-4-thiochromanyl-0,0- dimethyl-dithiophosphate being 0.0006 ppm. This concentration was sufficient to kill all larvae within 24 hours.

This concentration is only l/2,000 of that killing fish (for example, Lebiszes reii'cularus and Xiphophorus helleri), and l/l00,000 of that killing fish nutrition organisms (Daphnia magna) within the same period of time.

Phosphoric esters applied also as agents for combating mosquito larvae, for example fenitrothion, dursban, or dichlorvos, showed a higher degree of toxicity in the above fish (1/500 ratio). Thus, 6-fluoro4- thiochromanyl-0,0dimethyl-dithiophosphate can be employed with considerably reduced risks for fish in waters infested with fever mosquitoes.

EXAMPLE 59 In the manner described in Example 53, the compound 6-chloro-4-thiochromanyl-0,0-diethyldithiophosphate was tested on a phosphoric ester resistant strain of the European red mite (Meratetranychus ulmi). A! a concentration of 0.006 weight of active substance, all mobile and immobile stages of the mite population were killed.

Also the phosphoric esters tested again as a comparison has no effect when used in the concentrations indi cated in Example 53.

EXAMPLE 60 In the manner described in Example 54, the corn poumd 6-chloro-4-thiochromanyl-0,0-dimethyldithiophosphate was tested on the African cotton stainer. All bugs were killed at a concentration of 0.003 weight of active substance in the spray liquor.

EXAMPLE 61 3 to 4 Weeks old grain weevils (Calandra gmnaria) were treated, as described in Example 40, with an aqueous suspension ofa wettable powder of 6 fluoro-4- thiochromanyl-0,0-dimethyldithiophosphate. 0.003 mg of active substance per cm resulted in a mortaility rate after 48 hours.

EXAMPLE 62 In the manner described in Example 57, the compound 6-fluoro-4-thiochromanyl-0,0-diethyldithiophosphate as aqueous dilution of an emulsifiable concentrate was tested on larvae of the mealworm. After 48 hours, all test insects were killed at a concentration of 0005 Weight or 0.003 mg/cm of active substance.

EXAMPLE 63 In the manner described in Example 52, 6-chloro-4- thiochromanyl-0,0-diethyl'dithiophosphate (A) as aqueous suspension of a wettable powder and 6-chlor0 4-thiochromany1-0,0-diethylthiophosphate (B) as emulsion were tested on larvae of the Mexican bean beetle. Both substances gave excellent results in combating beetle larvae. After 48 hours, a 100% mortality rate was obtained using 0.0006 mg of active substance per cm in the case of A) and 0.0012 mg of active substance per cm in the case of (B).

EXAMPLE 64 In the manner described in Example 54, 6-rnethoxy 4-thiochromanyl 0,0-diethyl-dithiophosphate was tested as spray liquor on the American milkweed bug (Oncopellus fasciatus). All bugs were killed at a concentration of 0.006 weight of active substance.

EXAMPLE 65 l ml each of a suspension of nematodes comprising all development stages (Meloidogyne incognita), which had been dyed in a 0.1% acridine orange solution, was introduced into an aqueous medium containing differ ent concentration amounts of 4 thiochromanyl-0,0- dimethyl-dithiophosphate as active substance.

After 72 hours the percent mortality was determined by means of a fluorescence microscope. The test compound containing 0.3 weight of active substance had an activity three times that of the known compound carbofuran applied in a comparative test.

EXAMPLE 66 In vitro test on ticks of the Boophilus species I. Boophilus microplus a. strain of normal sensitivity b. Biarra strain, resistant c. Mackay strain, resistant 2. Boophilus decoloratus, resistant strain For the preparation of a suitable formulation, l parts by weight of active substance were dissolved in 100 parts by volume of a mixture of cyclohexanone and nonylphenol [0 E0, 8: l and the emulsifiable concentrate so obtained was diluted with water to obtain the desired concentration. l0 Adult female ticks of the cited species and different sensitivity to phosphoric esters, which had sucked themselves full of blood, were dipped for minutes into these dilutions. Subsequently, the ticks were sticked with their dorsal side onto an adhesive tape and kept in a warming closet (28 C, about 80% of relative air moisture) for the oviposition. Two weeks after treatment the activity of the formulations was determined by evaluating the inhibition of oviposition expressed in percent; l00% inhibition 20 meaning that all ticks treated with one active substance concentration did not oviposit, 0% meaning that all ticks did oviposit.

Table I In vitro test on ticks of different phosphoric ester sensitivity.

Inhibition of ovipoflitioninfi p Concentra- "5"KTZ'"'T""E B ..x- Active substance Hon of 00p 1 us mlcrop us oophilus ample active ,6tra; or 3& Mackay decolorattzs t i nOImE SenBll- 5 Tall] t s tivitg (resistant) (r s l i nt) (resistant) 0.2 70 90 90 20 s-Pwca 0.05 60 90 90 1 0.012 50 90 s 0 0,006 50 90 60 0 0.2 0 10 10 EC 2 S-P(CC2I-I5)2 0.05 0 0 0 0.012 90 0 10 20 0.006 0 0 0 s 0 Q 0.2 100 100 so 100 5 )2 0.05 100 20 100 0.012 100 10 0 100 0 006 100 0 0 0 E 0.2 100 40 so 7 F s-ptoc n 12g 1 2 i L J m 0,006 70 o 0 0 E, 0.2 100 100 sc 0' 90 90 90 90 9 Pm 2H5 )2 81052 90 90 20 90 m 0,006 90 0 10 50 E? 0.2 100 100 90 100 5-? 0 H 0.05 100 90 90 100 12 C1 C2 0.012 100 70 90 100 0.006 70, 40 50 100 9 0.2 100 90 100 100 an Br -Pt H 0. 05 90 so 0 100 0.012 90 70 70 100 0.005 90 60 50 60 Table I (continued) In vitro test on ticks of different phosphoric ester sensitivity.

Inhibition of ovipoeitioninfi E Concentra- T T "f x- Acuve subcavce on of Boophllus mlcroplus Boophilus am 1: dec atus p active sum i i l Macaay o r t e i norma senel S T5111 12 S tivity V (resistant) [r si infl (resistant) 0.2 100 so 100 90 Cl 5-?(00 H5 )2 0. 05 100 70 40 CH O. 012 90 O O 10 I 5 O, 006 5O 0 l0 0 5 8.2 100 39 j 5-? G3 2 5 105 5 0.012 100 l 3/ 0.006 0 0.2 100 h -1 (oc: a 0.05 70 3 0.012 0 0,005 O l s CH l S ry 0,2 100 l b7 i-: s-P(0c H 0.05 9 O.C12 80 0,006 0 5 fw 0.2 100 100 100 90 O/N/.Cl 0,05 90 O 10 0 012 100 40 0 0 (H C 0) P=S known 0,006 90 20 0 0 C1 0 2 100 SD v m 0,05 90 so 0 0 0 0.012 10 I 2 5 )2 kiown O. 005 2D 0 EXAM E 67 unfed bedbugs (Cimex lecrularius) each were placed for blood-sucking 0n the shaved abdominal skin of the guinea pigs.

The mortality rate of the test insect groups fed on the treated guinea pigs was evaluated until up to 24 hours after blood intake. The activity was l00% if all test insects had been killed within a certain time after the absorption of blood; it was zero if all test insects of a group were still living.

Table II Systemic activity in animals/guinea pigs Dose hrs after treatment: 76 mortality after 23's. Active substance mg/kg put on for blood- 1 suckin 1 2 D 4 5 e 7 8 2 comparison 0 O O O O O O O O 1 O 0 4O 90 100 3 O 10C 100 7 20 100 24 1O 10 30 100 48 O O O D O O O O O 5 comparison 0 O O 0 O O O O O l O O 40 9O 103 .1 SJHOCHQZ 5O 3 0 0 0 20 40 ll 7 O 100 s 24 0 O O D O O O O O 48 D O O O O O O O 0 comparison 0 O O O O O C O O l O O O O O O O O 100 25 3 C 90 100 7 O 100 24 O O O O O O O O O 48 O O O O 0 O O O O 21 22 Table II (continued) Systemic activity in animals/guinea pigs Dose hrs after treatmen' 7 mortality after hrs. Active substance mg/kg put on for bloodsuckin 1 l 2 D 4 5 5 7 8 2L 5 I s MUCH com lnrlson 8 10g O 0 O O 0 0 7 O O O 0 O O O O O ca comparison 0 o 0 o o 0 o o o 1 100 s 100 3 100 H T 0 100 s-P(ocII )2 24 o 0 o o o o o o 0 C1 comparison 0 O o 0 O O O O o 1 0 O O O O O O O O 50 5 C 7 100 24 O O O O O O O O 0 comparison 0 O O O O 0 O O C R0 100 O 3 O O O O O O n 7 C O O O O O O O 0 ccl -c'r:-P(ocii 031 comparison 0 O O O 0 O O O O 25 9O 90 100 i 3 0 O O 0 O 0 7 Q 0 o o 0 o o o 0 comparison 0 0 0 O O O O O 0 5O 1 O 100 ,vv 5 O 100 Son; 7 O 100 n S c a is o 0 o o o 0 0 o o n n omp r on ch c-1=(ocH 1 0 o 0 o o o o 0 50 25 3 o 100 HZlOf-Tl 7 O 100 Toxicological data Thiochromunylphosphoric acid esters 40 R3 R4 R5 R7 are hydrogen or alkyl havmg m one to four carbon atoms; at least three of the radl 4-thi0chromanyHLO-dimcthyl cals R3 l0 R1 being hydrogen;

LD 50 10 mg/kg morally R81 R9 are hydrogen. halogen, alkyl or alkoxy each fi-chlum-4-ihmchroman l-oo having from one to four carbon atoms;

diclhyl-dithiophosphatc LD 50 63-200 mg/kg ragra X i Oxygen or lf b-chloru-4-thio hmman l-(my 2. A compound as in claim 1 which is S-(6-fluoro-4- y p p LD Nil-630 fa! thiochromanyl)-0,0-dimethyl-dithiophosphatei many 3. A com ound as in claim I which is S-(6-fluoro-4 p l we claim; thlochromanyl)-O,O-d1ethyl-d1thiophosphate. L A compound of the formula A compound as n claim which 18 S-(6-chl0ro-4- X R thiochromanyl)-0,0-d1cthyl-dlthiophosphate.

O 1 5. A com ound as in claim 1 which is S-(6chloro-4 u p 5 P thlochromanyl )-0,0-diethyl-thiolphosphate.

R 6. A com ound as in claim 1 which is S-(7-bromo-4- R 2 P 7 Y 6 5 thiochromany])-(),0-dlethyl-dlthiophosphatei 5 4 7. A com ound as in claim 1 IS S (4-th1ochroman '1)- P 3 S /R;: 0,0-dimethyl-thiolphosphate. R 8. A compound as in claim 1 which is S (6-chloro-4- J thiochromanyl)-0,0-dimcthyl-thiolphosphate. Where!" 9. A compound as in claim 1 which is S(6-bromo-4- R and R are alkyl having from one to six carbon lhiochromanyl)O O-dimcthyl-thiolphosphutc.

atoms; 

1. A COMPOUND OF THE FORMULA
 2. A compound as in claim 1 which is S-(6-fluoro-4-thiochromanyl)-0,0-dimethyl-dithiophosphate.
 3. A compound as in claim 1 which is S-(6-fluoro-4-thiochromanyl)-0,0-diethyl-dithiophosphate.
 4. A compound as in claim 1 which is S-(6-chloro-4-thiochromanyl)-0,0-diethyl-dithiophosphate.
 5. A compound as in claim 1 which is S-(6-chloro-4-thiochromanyl)-0,0-diethyl-thiolphosphate.
 6. A compound as in claim 1 which is S-(7-bromo-4-thiochromanyl)-0,0-diethyl-dithiophosphate.
 7. A compound as in claim 1 is S-(4-thiochromanyl)-0,0-dimethyl-thiolphosphate.
 8. A compound as in claim 1 which is S-(6-chloro-4-thiochromanyl)-0,0-dimethyl-thiolphosphate.
 9. A compound as in claim 1 which is S-(6-bromo-4-thiochromanyl)-0,0-dimethyl-thiolphosphate. 